The cornea is the principal refractive element in the eye; its optical qualities are determined by its shape and its transparency. Corneal epithelial edema and stromal edema can independently or collectively degrade visual acuity. In this application we focus on the metabolic features of the corneal epithelium as they relate to the maintenance of corneal clarity, examine the interrelationships of other cells in the cornea to epithelial function, and attempt to refine our mathematical model to understand the functional reaction of the cornea to environmental perturbations. Transport and permeability properties will be studied with microelectrode techniques, radioactive tracer measurements, ion substitutions, pharmacological procedures, short-circuit current technique, ultrastructural techniques, thickness measurements, and computer simulation based on nonlinear irreversible thermodynamics. The mechanism of epithelial Cl transport will be studied in detail by determining the kinetics of the membrane "pump" and the role of paracellular pathways. A mathematical model for corneal hydration dynamics will be extended to include the effects of unstirred layers in cell cytoplasm and in bathing media. With this extension the phenomenological permeability coefficients of the corneal membranes will be determined for a variety of solutes. Specific biochemical events and membrane consequences of new pharmacological probes will be studied to provide a more detailed model for the sequence of events linking receptor activation and the specific increase in epithelial membrane Cl- conductance. The influence of sympathetic and sensory innervation on epithelial transport will be studied. Neuroanatomical mapping procedures will be used to document the presence and geographical distribution of sympathetic fibers in the rabbit and squirrel monkey corneas. The effect of sensory denervation on epithelial transport and barrier properties will be studied. The effects of diffusible proteins derived from cell cultured neurons on restoration of epithelial barrier properties after sensory denervation will be examined.